Areca-treated fibroblasts enhance tumorigenesis of oral epithelial cells.
Several hundred million Asians chew areca nut, which is strongly associated with oral carcinogenesis in people of this region. The impacts of areca nut extract on oral target cells are largely unclear. This study hypothesized an inductive role for areca-nut-exposed stromal cells in the progression of oral carcinomas in an at-risk population. Oral fibroblasts with chronic subtoxic areca nut extract treatment exhibited growth arrest and MMP-2 activation. The supernatant of arrested oral fibroblasts activated the AKT signaling pathway in oral carcinoma cells. The enhancement of proliferation, migration, and anchorage-independent growth of oral carcinoma cells elicited by such supernatant could be abrogated by blockers against MMP-2 or AKT. Subcutaneous co-injection of arrested oral fibroblasts into nude mice significantly enhanced the tumorigenicity of xenographic oral carcinoma cells. This study concludes that areca nut extract may impair oral fibroblasts and then modulate the progression of oral epithelial oncogenesis via their secreted molecules.
Lu
H-H
HH
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, No. 155, Li-Nong St., Sec.2, Taipei, Taiwan.
Liu
C-J
CJ
Liu
T-Y
TY
Kao
S-Y
SY
Lin
S-C
SC
Chang
K-W
KW
D000818:Animals; D001114:Areca / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced*; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000139:chemically induced*; D010936:Plant Extracts / Q000009:adverse effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017077:Culture Media, Conditioned; D010936:Plant Extracts; D019715:Tissue Inhibitor of Metalloproteinase-1; D051057:Proto-Oncogene Proteins c-akt; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2